PROJECT SUMMARY/ABSTRACT Most Americans experience some form of musculoskeletal pain in their lifetime and painful myofascial Temporomandibular Disorder (mTMD) is one condition affecting at least 10% of community women. The causes of mTMD are poorly understood. Patients are often left with expensive or invasive treatments for which evidence of efficacy is mixed at best. Persistent mTMD is increasingly considered a chronic pain condition, with a presumed dysfunction in a central pain mechanisms such as in endogenous pain modulation. Despite increasing research, including use of quantitative sensory testing, conclusive evidence of pathology has not emerged. Given the complexity of human neurobiology, including the inherently dynamic and stimulus- dependent nature of endogenous pain modulation, lack of progress may be due to unmeasured confounding. This proposal will use an innovative approach to address potential confounding introduced by phenotypic heterogeneity and nociceptive burden. First, phenotypes of mTMD based on presence of joint pain, i.e. muscle only-based pain (M-pain) versus both muscle and joint-based pain (MJ-pain) will be refined to determine case groups. Second, unmeasured nociceptive input from other potential sources, (i.e., nociceptive burden) will be addressed by examining both comorbidities that represent peripheral sensitization and laboratory-based sleep masticatory muscle activity. To conduct a more valid examination of the role of endogenous pain modulation dysfunction in mTMD, the following aims will be examined first in a completed case-control dataset of women, and second in planned pilot research: (1) Explore characteristics of temporomandibular joint pain to classify mTMD patients as M-pain or MJ-pain and examine patterns of comorbid disorders; (2) Compare facilitatory pain modulation among the M-pain, MJ-pain and control groups; and (3) Compare inhibitory pain modulation among M-pain, MJ-pain and control groups. To accomplish the proposed research and develop a research agenda that can uncover mechanisms of mTMD, the present application for a Mentored Research Scientist Development Award to Promote Diversity in Dental, Oral and Craniofacial Research Workforce (K01) proposes to advance the expertise of a trained psychiatric epidemiologist in four areas: (1) chronic pain taxonomy (clinical and research); (2) neuroscience of pain and translational research; (3) psychophysics of pain; and secondarily (4) systems science approaches for the study of chronic pain. The proposed research and training will result in submission of an R01 grant proposal on mechanisms of myofascial pain onset and maintenance in human subjects.